Exam 6: Principles of Gene Regulation and Epigenetics

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1) Chromosome microdeletion (for example of the maternal 15q11-13 region in Angelman syndrome and the paternal 15q11-13 region in Prader-Willi syndrome)
2) Uniparental disomy. The normally expressed allele is not inherited; instead, both copies of a chromosome with the silenced allele come from one parent. Examples include: maternal disomy 15 in the case of Prader Willi syndrome; paternal disomy 15 in the case of Angelman syndrome; and maternal disomy 11 or maternal disomy 17 in the case of Silver-Russell syndrome.
3) Hypomethylation of imprinting control region (ICR). At the imprinted gene cluster at 11p15, the ICR1 control region is methylated on paternal chromosome 15, and that allows distant enhancer sequences to activate expression of the IGF2 gene. Sometimes, however, there is a reduction in methylation at ICR1 on the paternal chromosome, and it is now bound by the CTCF protein which activates the assembly of an insulator region that prevents the remote enhancers from activating IGF2.
4) Inactivating point mutations in the normally active allele